274 research outputs found

    Effects of formalin fixation on polarimetric properties of brain tissue: fresh or fixed?

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    Imaging Mueller polarimetry (IMP) appears as a promising technique for real-time delineation of healthy and neoplastic tissue during neurosurgery. The training of machine learning algorithms used for the image post-processing requires large data sets typically derived from the measurements of formalin-fixed brain sections. However, the success of the transfer of such algorithms from fixed to fresh brain tissue depends on the degree of alterations of polarimetric properties induced by formalin fixation (FF). Comprehensive studies were performed on the FF induced changes in fresh pig brain tissue polarimetric properties. Polarimetric properties of pig brain were assessed in 30 coronal thick sections before and after FF using a wide-field IMP system. The width of the uncertainty region between gray and white matter was also estimated. The depolarization increased by 5% in gray matter and remained constant in white matter following FF, whereas the linear retardance decreased by 27% in gray matter and by 28% in white matter after FF. The visual contrast between gray and white matter and fiber tracking remained preserved after FF. Tissue shrinkage induced by FF did not have a significant effect on the uncertainty region width. Similar polarimetric properties were observed in both fresh and fixed brain tissues, indicating a high potential for transfer learning

    Plasmodium falciparum merozoite surface protein 2: epitope mapping and fine specificity of human antibody response against non-polymorphic domains.

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    BACKGROUND: Two long synthetic peptides representing the dimorphic and constant C-terminal domains of the two allelic families of Plasmodium falciparum merozoite surface proteins 2 are considered promising malaria vaccine candidates. The aim of the current study is to characterize the immune response (epitope mapping) in naturally exposed individuals and relate immune responses to the risk of clinical malaria. METHODS: To optimize their construction, the fine specificity of human serum antibodies from donors of different age, sex and living in four distinct endemic regions was determined in ELISA by using overlapping 20 mer peptides covering the two domains. Immune purified antibodies were used in Western blot and immunofluorescence assay to recognize native parasite derivate proteins. RESULTS: Immunodominant epitopes were characterized, and their distribution was similar irrespective of geographic origin, age group and gender. Acquisition of a 3D7 family and constant region-specific immune response and antibody avidity maturation occur early in life while a longer period is needed for the corresponding FC27 family response. In addition, the antibody response to individual epitopes within the 3D7 family-specific region contributes to protection from malaria infection with different statistical weight. It is also illustrated that affinity-purified antibodies against the dimorphic or constant regions recognized homologous and heterologous parasites in immunofluorescence and homologous and heterologous MSP2 and other polypeptides in Western blot. CONCLUSION: Data from this current study may contribute to a development of MSP2 vaccine candidates based on conserved and dimorphic regions thus bypassing the complexity of vaccine development related to the polymorphism of full-length MSP2

    Plasmodium vivax and Plasmodium falciparum infection dynamics: re-infections, recrudescences and relapses

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    Background: In malaria endemic populations, complex patterns of Plasmodium vivax and Plasmodium falciparum blood-stage infection dynamics may be observed. Genotyping samples from longitudinal cohort studies for merozoite surface protein (msp) variants increases the information available in the data, allowing multiple infecting parasite clones in a single individual to be identified. msp genotyped samples from two longitudinal cohorts in Papua New Guinea (PNG) and Thailand were analysed using a statistical model where the times of acquisition and clearance of each clone in every individual were estimated using a process of data augmentation. Results: For the populations analysed, the duration of blood-stage P. falciparum infection was estimated as 36 (95% Credible Interval (CrI): 29, 44) days in PNG, and 135 (95% CrI 94, 191) days in Thailand. Experiments on simulated data indicated that it was not possible to accurately estimate the duration of blood-stage P. vivax infections due to the lack of identifiability between a single blood-stage infection and multiple, sequential blood-stage infections caused by relapses. Despite this limitation, the method and data point towards short duration of blood-stage P. vivax infection with a lower bound of 24 days in PNG, and 29 days in Thailand. On an individual level, P. vivax recurrences cannot be definitively classified into re-infections, recrudescences or relapses, but a probabilistic relapse phenotype can be assigned to each P. vivax sample, allowing investigation of the association between epidemiological covariates and the incidence of relapses. Conclusion: The statistical model developed here provides a useful new tool for in-depth analysis of malaria data from longitudinal cohort studies, and future application to data sets with multi-locus genotyping will allow more detailed investigation of infection dynamics

    Impacts of 21st‐century climate change on montane habitat in the Madrean Sky Island Archipelago

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    Aim The Madrean Sky Island Archipelago is a North American biodiversity hotspot composed of similar to 60 isolated mountains that span the Cordilleran Gap between the Rocky Mountains and the Sierra Madre Occidental. Characterized by discrete patches of high-elevation montane habitat, these "sky islands" serve as stepping stones across a "sea" of desert scrub/grassland. Over this coming century, the region is expected to shift towards a warmer and drier climate. We used species distribution modelling to predict how the spatial distribution of montane habitat will be affected by climate change. Location Madrean Sky Island Archipelago, south-west United States and north-west Mexico (latitude, 29-34 degrees N; longitude, 107-112 degrees W). Methods To approximate the current distribution of montane habitat, we built species distribution models for five high-elevation species (Ceanothus fendleri, Pinus strobiformis, Quercus gambelii, Sciurus aberti, and Synuchus dubius). The resulting models were projected under multiple climate change scenarios-four greenhouse gas concentration trajectories (RCP 2.6, 4.5, 6.0, and 8.5) for each of three climate models (CCSM4, MPI-ESM-LR, and NorESM1-M)-to generate predicted distributions for the years 2050 and 2070. We performed chi-squared tests to detect any future changes to total montane habitat area, and Conover-Iman tests to evaluate isolation among the discrete montane habitat patches. Results While the climate models differ with respect to their predictions as to how severe the effects of future climate change will be, they all agree that by as early as year 2050, there will be significant montane habitat loss and increased montane habitat patch isolation across the Madrean Archipelago region under a worst-case climate change scenario (RCP 8.5). Main conclusions Our results suggest that under 21st-century climate change, the Madrean Sky Islands will become increasingly isolated due to montane habitat loss. This may affect their ability to serve as stepping stones and have negative implications for the region's biodiversity.University of Arizona Center for Insect ScienceOpen access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

    A Jurisprudential Analysis of Government Intervention and Prenatal Drug Abuse

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    This article takes a different approach in considering the problem of prenatal drug abuse. After briefly discussing government intervention and constitutional issues, this article will consider the concept of duty and correlative rights. This discussion of duty and correlative rights suggests that the government can take measures to curb prenatal drug use without recognizing fetal rights. The article concludes with a discussion of the utility of criminal legislation as compared to public health legislation that treats drug addiction as a disease requiring treatment. As formulated, the proposal for public health legislation is not based on any concept of fetal rights. Instead, it is based on the recognition of societal interests, as well as the woman’s needs

    Antibodies elicited in adults by a primary Plasmodium falciparum blood-stage infection recognize different epitopes compared with immune individuals

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    <p>Abstract</p> <p>Background</p> <p>Asexual stage antibody responses following initial <it>Plasmodium falciparum </it>infections in previously healthy adults may inform vaccine development, yet these have not been as intensively studied as they have in populations from malaria-endemic areas.</p> <p>Methods</p> <p>Serum samples were collected over a six-month period from twenty travellers having returned with falciparum malaria. Fourteen of these were malaria-naĂŻve and six had a past history of one to two episodes of malaria. Antibodies to seven asexual stage <it>P. falciparum </it>antigens were measured by ELISA. Invasion inhibitory antibody responses to the 19kDa fragment of merozoite surface protein 1 (MSP1<sub>19</sub>) were determined.</p> <p>Results</p> <p>Short-lived antibody responses were found in the majority of the subjects. While MSP1<sub>19 </sub>antibodies were most common, MSP1 block 2 antibodies were significantly less frequent and recognized conserved domains. Antibodies to MSP2 cross-reacted to the dimorphic allelic families and anti-MSP2 isotypes were not IgG3 skewed as shown previously. MSP1<sub>19 </sub>invasion inhibiting antibodies were present in 9/20 patients. A past history of malaria did not influence the frequency of these short-lived, functional antibodies (p = 0.2, 2-tailed Fisher's exact test).</p> <p>Conclusion</p> <p>Adults infected with <it>P. falciparum </it>for the first time, develop relatively short-lived immune responses that, in the case of MSP1<sub>19</sub>, are functional. Antibodies to the polymorphic antigens studied were particularly directed to allelic family specific, non-repetitive and conserved determinants and were not IgG subclass skewed. These responses are substantially different to those found in malaria immune individuals.</p
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